Over the past two years, scientific research has moved at an unprecedented rate in response to the COVID-19 pandemic. The rapid development of effective vaccines and therapeutics would not have been possible without extensive background knowledge on coronaviruses developed over decades by researchers, including Kathryn (Kay) Holmes. Kay’s research team discovered the first coronavirus receptors for mouse hepatitis virus and human coronavirus 229E and contributed a wealth of information on coronaviral spike glycoproteins and receptor interactions that are critical determinants of host and tissue specificity. She collaborated with several research laboratories to contribute knowledge in additional areas, including coronaviral pathogenesis, epidemiology, and evolution. Throughout her career, Kay was an extremely dedicated and thoughtful mentor to numerous graduate students and post-doctoral fellows. This article provides a review of her contributions to the coronavirus field and her exemplary mentoring.
Biotic homogenization—increasing similarity of species composition among ecological communities—has been linked to anthropogenic processes operating over the last century. Fossil evidence, however, suggests that humans have had impacts on ecosystems for millennia. We quantify biotic homogenization of North American mammalian assemblages during the late Pleistocene through Holocene (~30,000 ybp to recent), a timespan encompassing increased evidence of humans on the landscape (~20,000–14,000 ybp). From ~10,000 ybp to recent, assemblages became significantly more homogenous (>100% increase in Jaccard similarity), a pattern that cannot be explained by changes in fossil record sampling. Homogenization was most pronounced among mammals larger than 1 kg and occurred in two phases. The first followed the megafaunal extinction at ~10,000 ybp. The second, more rapid phase began during human population growth and early agricultural intensification (~2,000–1,000 ybp). We show that North American ecosystems were homogenizing for millennia, extending human impacts back ~10,000 years. Biotic homogenization, which is increased similarity in the composition of species among communities, is rising due to human activities. Using North American mammal fossil records from the past 30,000 years, this study shows that this phenomenon is ancient, beginning between 12,000 and 10,000 years ago with the extinction of the mammal megafauna.
Objectives The purpose of this study was to understand pregnant women’s perceptions of three validated substance use screening tools and identify a preferred tool for use during pregnancy. The three screening tools studied included the 4P’s Plus, the NIDA Quick Screen/ NIDA-Modified Alcohol, Smoking and Substance Involvement Screening Test, and the Substance Use Risk Profile-Pregnancy Scale. Methods A total of 493 cognitive interviews were completed with a diverse sample of pregnant women presenting to two obstetrics practices in Baltimore, MD from January 2017 to January 2018. This study served as a qualitative companion to a larger study comparing the accuracy and acceptability of substance use screening tools in prenatal care. After completing each screening tool, participants were asked their perceptions of the tool and to choose their preferred tool. Interviews were recorded, transcribed verbatim, coded, and analyzed using NVivo software. Results The plurality of participants (43.4%) reported they preferred the 4P’s Plus. Fewer participants preferred the NIDA Quick Screen (32.5%) and the SURP-P (24.1%). Participants felt that the 4P’s Plus was both comprehensive and concise. While many participants felt that disclosure of substance use would vary by individual, participants also suggested that when screening is confidential, includes questions about a patient’s background, and administered by a non-judgmental provider, pregnant people may be more likely to answer honestly. Conclusions for Practice The 4P’s Plus is a promising and acceptable substance use screening tool for use in prenatal care. Clinicians can use several methods to increase acceptability of substance use screening and encourage disclosure of prenatal substance use.
Nipah virus (NiV) disease is a bat-borne zoonosis responsible for outbreaks with high lethality and is a priority for vaccine development. With funding from the Coalition of Epidemic Preparedness Innovations (CEPI), we are developing a chimeric vaccine (PHV02) composed of recombinant vesicular stomatitis virus (VSV) expressing the envelope glycoproteins of both Ebola virus (EBOV) and NiV. The EBOV glycoprotein (GP) mediates fusion and viral entry and the NiV attachment glycoprotein (G) is a ligand for cell receptors, and stimulates neutralizing antibody, the putative mediator of protection against NiV. PHV02 is identical in construction to the registered Ebola vaccine (Ervebo) with the addition of the NiV G gene. NiV ephrin B2 and B3 receptors are expressed on neural cells and the wild-type NiV is neurotropic and causes encephalitis in affected patients. It was therefore important to assess whether the NiV G alters tropism of the rVSV vector and serves as a virulence factor. PHV02 was fully attenuated in adult hamsters inoculated by the intramuscular (IM) route, whereas parental wild-type VSV was 100% lethal. Two rodent models (mice, hamsters) were infected by the intracerebral (IC) route with graded doses of PHV02. Comparator active controls in various experiments included rVSV-EBOV (representative of Ebola vaccine) and yellow fever (YF) 17DD commercial vaccine. These studies showed PHV02 to be more neurovirulent than both rVSV-EBOV and YF 17DD in infant animals. PHV02 was lethal for adult hamsters inoculated IC but not for adult mice. In contrast YF 17DD retained virulence for adult mice inoculated IC but was not virulent for adult hamsters. Because of the inconsistency of neurovirulence patterns in the rodent models, a monkey neurovirulence test (MNVT) was performed, using YF 17DD as the active comparator because it has a well-established profile of quantifiable microscopic changes in brain centers and a known reporting rate of neurotropic adverse events in humans. In the MNVT PHV02 was significantly less neurovirulent than the YF 17DD vaccine reference control, indicating that the vaccine will have an acceptable safety profile for humans. The findings are important because they illustrate the complexities of phenotypic assessment of novel viral vectors with tissue tropisms determined by transgenic proteins, and because it is unprecedented to use a heterologous comparator virus (YF vaccine) in a regulatory-enabling study. This approach may have value in future studies of other novel viral vectors.
Electronic nicotine delivery systems (ENDS) continue to rapidly evolve. Current products pose unique challenges and opportunities for researchers and regulators. This commentary aims to highlight research gaps, particularly in toxicity research, and provide guidance on priority research questions for the tobacco regulatory community. Disposable flavoured ENDS have become the most popular device class among youth and may contain higher nicotine levels than JUUL devices. They also exhibit enhanced harmful and potentially harmful constituents production, contain elevated levels of synthetic coolants and pose environmental concerns. Synthetic nicotine and flavour capsules are innovations that have recently enabled the circumvention of Food and Drug Administration oversight. Coil-less ENDS offer the promise of delivering fewer toxicants due to the absence of heating coils, but initial studies show that these products exhibit similar toxicological profiles compared with JUULs. Each of these topic areas requires further research to understand and mitigate their impact on human health, especially their risks to young users.
EPA approved disinfectants for coronavirus lists many products for use on hard, non-porous materials. There are significantly less products registered for use on porous materials. Further, many common, high-touch surfaces fall in between non-porous materials such as glass and porous materials such as soft fabrics. The objective of this study was to assess the efficacy of selected commercially available disinfectant products against coronaviruses on common, high-touch surfaces. Four disinfectants (Clorox Total 360, Bleach solution, Vital Oxide, and Peroxide Multi-Surface Cleaner) were evaluated against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV in cell culture medium was inoculated onto four materials: stainless steel, latex-painted drywall tape, Styrene Butadiene rubber (rubber), and bus seat fabric. Immediately (T0) or 2-hours (T2) post-inoculation, disinfectants were applied by trigger-pull or electrostatic sprayer and either held for recommended contact times (Spray Only) or immediately wiped (Spray and Wipe). Recovered infectious MHV was quantified by median tissue culture infectious dose assay. Bleach solution, Clorox Total 360, and Vital Oxide were all effective (>3-log10 reduction or complete kill of infectious virus) with both the Spray Only and Spray and Wipe methods on stainless steel, rubber, and painted drywall tape when used at recommended contact times at both T0 and T2 hr. Multi-Surface Cleaner unexpectedly showed limited efficacy against MHV on stainless steel within the recommended contact time; however, it showed increased (2.3 times greater efficacy) when used in the Spray and Wipe method compared to Spray Only. The only products to achieve a 3-log10 reduction on fabric were Vital Oxide and Clorox Total 360; however, efficacy of Vital Oxide against MHV on fabric was reduced to below 3-log10 when applied by electrostatic sprayer compared to trigger-pull sprayer. This study highlights the importance of considering material, product, and application method when developing a disinfection strategy for coronaviruses on high-touch surfaces.
Background Increasing number of breast cancer survivors in the USA have led to greater focus on the long-term health outcomes and surveillance care among these women. However limited evidence exists of use of surveillance mammography among breast cancer survivors and how it varies across racial/ethnic groups. Methods We conducted a systematic review of the literature to explore disparities in use of surveillance mammogram among women breast cancer survivors by searching for relevant studies published between 2000 and 2020 from Medline (Ovid), PubMed (National Library of Medicine), and PsycINFO (Ovid) bibliographic databases. Two authors independently screened titles, abstracts, and full texts of all articles that reported surveillance mammography use across racial/ethnic groups. Data on study design, screening eligibility, sample size, operational definition, and/or measure of the use of a surveillance mammogram among breast cancer survivors and the association between race/ethnicity and use of a surveillance mammogram were summarized in the evidence tables. Results We identified 1544 records from the three databases, and 30 studies examined the use of surveillance mammograms among breast cancer survivors across race/ethnic groups. Of these, 21 provided adjusted estimates of racial/ethnic disparities in use of surveillance mammograms, and 15 of these reported statistically significant disparities. In summary, most studies reported that non-white women (mainly Blacks and Hispanics) were less likely to receive a timely surveillance mammogram compared to White. Conclusion This study extends the evidence of racial/ethnic disparities beyond completion of initial treatment by finding similar disparities in receipt of surveillance mammograms among breast cancer survivors. Implication for Cancer Survivors Our findings identify a need to improve efforts to increase post-treatment use of surveillance mammography among racial/ethnic minority women to reduce these gaps and improve overall clinical and quality of life outcomes.
To increase the use of biofuels in diesel engines and reduce harmful emissions emitted from diesel fuel, biodiesel and higher alcohols are fuel sources at the forefront of research. The aim of this study is to understand the effect of water-containing n-butanol-biodiesel blends on regulated emissions, emphasizing nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs), which are harmful for the environment and engine durability. 10% n-butanol (B90Bu10) and 10% n-butanol-1% water (B89Bu10W1) were blended with 89% waste-oil biodiesel and tested in a diesel engine at four engine loads at a constant engine speed. PAH samples were analyzed using gas chromatography-mass spectrometry (GC-MS). Results showed B100, B90Bu10 and B89Bu10W1 blends increased break specific fuel consumption (BSFC), exhaust gas temperatures (EGT), carbon monoxide (CO) and hydrocarbon (HC) emissions. However, NOx emissions significantly decreased using butanol and butanol-water blends. Compared to diesel, biodiesel and blended fuels significantly reduced total PAHs and PAH toxicity up to 75.0%. However, B89Bu10W1 increased total PAH and PAH toxicity by 35.7%. Overall, the biodiesel-butanol blend, which emits less carcinogenic pollutants and low-cyclic PAHs than water-containing fuel, was found to reduce the risk of wetstacking in diesel engines operating under low loads.
To standardize materials and component characterization for next generation hydrogen production and energy generation solid oxide cell (SOC) technologies, test protocols are being established to facilitate comparison across the numerous laboratories and research institutions where SOC development for application in solid oxide fuel cells (SOFCs) and solid oxide electrolyzes cells (SOEC) is conducted. This paper proposes guiding protocols for fundamental electrical properties characterization of SOC materials, including temperature- and oxygen partial pressure (pO2)-dependent conductivity measurements, and use of the electromotive force for determining the transference numbers, or contributions of each charge carrier (i.e., ions and electrons), to the total conductivity. The protocol for Archimedes density measurements is also provided as an integral technique to both of these methods.
A comprehensive quantitative risk assessment for the construction and operation of CO2 transportation networks considered for the Midcontinent United States was conducted. The results showed risks associated with CO2 pipelines were significantly less than those of other pipeline types. The assessment used four conceptual pipelines of different lengths to discuss risks operators may see. The assessment evaluated the risk associated with construction and operation using data from the US Occupational Safety Health Administration to determine the risk of injury or death for pipeline workers and data from the US Pipeline and Hazardous Materials Safety Administration for CO2, natural gas distribution, natural gas transmission/gathering, and non-CO2 hazardous liquid pipelines to develop quantitative likelihood and severity values leading to risk values. The data for the assessment covered incidents from 2010 to 2017 for CO2 pipelines. The average risk for construction and 30 years of operation for four CO2 pipeline configurations ranging between 79 and 1,546 miles in length was found. The construction and operational risk averaged between $1,400,521 (approximately $0.02/tonne of CO2) for the shorter pipeline (79 miles) and $27,481,939 (approximately $0.10/tonne of CO2) for a longer pipeline (1,546 miles). The largest risks of fatality for CO2 pipelines comes from vehicle transport. The largest operational risk to the pipeline was due to leakage. Public pipeline opposition is also a significant risk; it was not quantified but is addressed.
Optimal use of Hierarchical Bayesian Model (HBM)-assembled aerosol optical depth (AOD)-PM2.5 fused surfaces in epidemiologic studies requires homogeneous temporal and spatial fused surfaces. No analytical method is available to evaluate spatial heterogeneity. The temporal case-crossover design was modified to assess the spatial association between four experimental AOD-PM2.5 fused surfaces and four respiratory–cardiovascular hospital events in 12 km2 grids. The maximum number of adjacent lag grids with significant odds ratios (ORs) identified homogeneous spatial areas (HOSAs). The largest HOSA included five grids (lag grids 04; 720 km2) and the smallest HOSA contained two grids (lag grids 01; 288 km2). Emergency department asthma and inpatient asthma, myocardial infarction, and heart failure ORs were significantly higher in rural grids without air monitors than in urban grids with air monitors at lag grids 0, 1, and 01. Rural grids had higher AOD-PM2.5 concentration levels, population density, and poverty percentages than urban grids. Warm season ORs were significantly higher than cold season ORs for all health outcomes at lag grids 0, 1, 01, and 04. The possibility of elevated fine and ultrafine PM and other demographic and environmental risk factors synergistically contributing to elevated respiratory–cardiovascular chronic diseases in persons residing in rural areas was discussed.
Epidemiologic evidence indicates exposure to polyfluoroalkyl substances (PFAS) influences immunosuppression, with diminished vaccination response. The relationship between PFAS blood levels and coronavirus disease 2019 (COVID-19) occurrence by age warrants further examination. This assessment identified blood PFAS exposure levels in discrete populations. Recent PFAS population studies summarizing age and gender results were identified and included. Geographically corresponding COVID-19 incidence data were determined for selected counties in North Carolina (NC) and Ohio (OH), and the state of New Jersey (NJ). Centers for Disease Control and Prevention COVID-19 databases were accessed for national incidence data by age groupings. We assessed associations between blood PFAS concentrations, COVID-19 incidence rates, and key demographic characteristics, within subpopulations. COVID-19 incidence counts and blood PFAS concentration were obtained for each age group, along with estimated U.S. Census total population. A general trend observed is higher PFAS levels in older age groups. Younger age groups contained fewer COVID-19 cases. Global COVID-19 mortality is highest in elderly populations with hospitalization and death greatly increasing from age 50. PFAS exposures occurring early in life may cause deleterious health effects later in life, including decreased antibody response and reduced disease resistance. Highest levels of both PFAS exposure and COVID-19 were found in the oldest populations. While this does not determine causality, such associations should help promote further study.
Introduction: Although the Food and Drug Administration banned other characterising flavours in cigarettes, menthol cigarettes are still available to consumers. Young adult new smokers are initiating with menthol cigarettes, such that the prevalence of young adults menthol versus non-menthol smokers is increasing. Experimentation with menthol cigarettes is associated with progression to regular smoking and nicotine dependence. This ongoing clinical trial in young adult smokers measures appeal and the reinforcing value of smoking menthol versus non-menthol cigarettes and the impact of these variables on changes in smoking behaviour at a 6-month follow-up. Methods and analysis: Reinforcement for menthol smoking is assessed in the laboratory using a validated behavioural economic choice task, and appeal is measured in the natural environment using ecological momentary assessment (EMA). Analyses will examine differences between menthol and non-menthol cigarette smoking on measures of subjective response in the laboratory and via EMA, and how subjective response mediates the association between menthol preference at baseline and smoking outcomes at follow-up. Ethics and dissemination: This protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (#10581). The findings will isolate the unique effects of menthol in smoking and will help inform regulatory decisions about the abuse liability of menthol cigarettes. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences. Trial registration number: NCT03953508.
The application of stabilization technologies to a radiologically contaminated surface has the potential for reducing the spread of contamination and, as a result, decreasing worker exposure to radiation. Three stabilization technologies, calcium chloride (CaCl2), flame retardant Phos-Chek® MVP-Fx, and Soil2OTM were investigated to evaluate their ability to reduce the resuspension and tracking of radiological contamination during response activities such as vehicle and foot traffic. Concrete pavers, asphalt pavers, and sandy soil walking paths were used as test surfaces, along with simulated fallout material (SFM) tagged with radiostrontium (Sr-85) applied as the contaminant. Radiological activities were measured using gamma spectrometry before and after simulated vehicle operation and foot traffic experiments, conducted with each stabilization technology and without application as a nonstabilized control. These measurements were acquired separately for each combination of surface and vehicle/foot traffic experiment. The resulting data describes the extent of SFM removed from each surface onto the tires or boots, the extent of SFM transferred to adjacent surfaces, and the residual SFM remaining on the tires or boots after each experiment. The type of surface and response worker actions influenced the stabilization results. For instance, when walked over, less than 2% of particles were removed from nonstabilized concrete, 4% from asphalt, and 40% of the particles were removed from the sand surface. By contrast, for vehicle experiments, ~40% of particles were again removed from the sand, but 7% and 15% from concrete and asphalt, respectively. In most cases, the stabilization technologies did provide improved stabilization. The improvement was related to the type of surface, worker actions, and stabilizer; a statistical analysis of these variables is presented. Overall, the results suggest an ability to utilize these technologies during the planning and implementation of response activities involving foot and vehicle traffic. In addition, resuspension of aerosolizable range SFM was monitored during walking path foot traffic experiments, and all stabilizing agents decreased the measured radioactivity, with the Soil2OTM decrease being 3 fold, whereas the CaCl2 and Phos-Chek MVP-Fx surfaces generated no detectable radioactivity. Overall, these results suggest that the stabilization technologies decrease the availability of particles respirable by response workers under these conditions.
Intracortical brain–machine interfaces decode motor commands from neural signals and translate them into actions, enabling movement for paralysed individuals. The subjective sense of agency associated with actions generated via intracortical brain–machine interfaces, the neural mechanisms involved and its clinical relevance are currently unknown. By experimentally manipulating the coherence between decoded motor commands and sensory feedback in a tetraplegic individual using a brain–machine interface, we provide evidence that primary motor cortex processes sensory feedback, sensorimotor conflicts and subjective states of actions generated via the brain–machine interface. Neural signals processing the sense of agency affected the proficiency of the brain–machine interface, underlining the clinical potential of the present approach. These findings show that primary motor cortex encodes information related to action and sensing, but also sensorimotor and subjective agency signals, which in turn are relevant for clinical applications of brain–machine interfaces.
In this paper, we investigated the interplay of rock deformation, micro-crack development, and fluid flow response using a stress-dependent pore network model. This model incorporates a representation of grains and cements interactions to enable predictions of the mechanical response from micro-scale elements. To complete the model, fluid flow response is modeled using a network of the pores between grains. Due to applying stress, numerically built rock sample deforms, and possible micro-cracks develop across the sample. The original pore network is re-built to estimate changes in fluid flow properties of the rock sample. We studied the effect of grains stiffness on the transport properties of the Berea sandstone sample as a function of deformation. The effect of intragranular bond breakage on changes in the permeability of Berea sandstone in a hydrostatic numerical test was also investigated. We performed numerical triaxial tests to investigate rock failure mechanisms during loading at two (high and low) confining pressures. The model enables studying transport behavior of intact rocks as a function of deformation, the role of intragranular bond breakage on permeability evolution of high-porosity rocks, and the relationship between joint deformation and permeability enhancement through applying the stress-dependent pore network model. We also show that confining pressure significantly affects formation of different failure modes and has a major role on the transport response of rocks after failure. Modeling results indicate the impact of micro-mechanical phenomena associated with the intact and the jointed rock deformation and failure on permeability changes. Article highlights A stress-dependent pore network model was applied to estimate permeability changes during rock deformation and failure. Modeling intragranular bond breakage shows permeability decrease during the Berea sample rock failure (in agreement with experimental measurements). Permeability increase observed after jointed rock failure due to joint dilation in contrast to permeability decrease during intact rock failure.
Given the rapid pace of modern technological advancements, the public should expect and demand measurable improvements to highway safety. Yet, it is not so clear how much improvement may be anticipated. Government organizations such as the U.S. Department of Transportation (U.S. DOT) and National Highway Traffic Safety Administration (NHTSA) have already spent decades and millions of dollars researching proper markings, alerting systems, and safety distances to help reduce collisions and other incidents on public roadways. While clearly this effort has had great impact, there are limiting factors that continually constrain the ability of traditional methods to significantly reduce the number of collisions. Such factors include driver behavior aspects such as reaction time, sudden maneuvers, and traffic violations, plus infrastructure aspects such as malfunctioning signals, inadequate signage, and non-standard road design. As increased numbers of connected and automated vehicles (CAV) are introduced into the traffic stream, and advanced safety applications are continually improving, the industry envisions a major decline in incidents across the board. This paper details the limiting factors to why a sizable reduction of incidents is not possible with conventional resources and introduces the framework for adding advanced warnings into connected safety applications in existing vehicles, such as red-light violation warning (RLVW), to achieve measurable results. Further, the paper then applies this same model for use within automated driving systems (ADS). More than just a technological examination, this paper also predicts the expected impact to roadway incidents.
For brain–computer interfaces (BCIs) to be viable for long-term daily usage, they must be able to quickly identify and adapt to signal disruptions. Furthermore, the detection and mitigation steps need to occur automatically and without the need for user intervention while also being computationally tractable for the low-power hardware that will be used in a deployed BCI system. Here, we focus on disruptions that are likely to occur during chronic use that cause some recording channels to fail but leave the remaining channels unaffected. In these cases, the algorithm that translates recorded neural activity into actions, the neural decoder, should seamlessly identify and adjust to the altered neural signals with minimal inconvenience to the user. First, we introduce an adapted statistical process control (SPC) method that automatically identifies disrupted channels so that both decoding algorithms can be adjusted, and technicians can be alerted. Next, after identifying corrupted channels, we demonstrate the automated and rapid removal of channels from a neural network decoder using a masking approach that does not change the decoding architecture, making it amenable for transfer learning. Finally, using transfer and unsupervised learning techniques, we update the model weights to adjust for the corrupted channels without requiring the user to collect additional calibration data. We demonstrate with both real and simulated neural data that our approach can maintain high-performance while simultaneously minimizing computation time and data storage requirements. This framework is invisible to the user but can dramatically increase BCI robustness and usability.
People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors.
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